Effects of Ganoderma lucidum polysaccharide peptide ameliorating cyclophosphamide-induced immune dysfunctions based on metabolomics analysis

Jing Xie; Dongmei Lin; Jing Li; Tonghui Zhou; Shuqian Lin; Zhanxi Lin

doi:10.3389/fnut.2023.1179749

Effects of Ganoderma lucidum polysaccharide peptide ameliorating cyclophosphamide-induced immune dysfunctions based on metabolomics analysis

Front Nutr. 2023 May 25:10:1179749. doi: 10.3389/fnut.2023.1179749. eCollection 2023.

Authors

Jing Xie^{1

2

3}, Dongmei Lin², Jing Li², Tonghui Zhou², Shuqian Lin², Zhanxi Lin^{1

2}

Affiliations

¹ College of Food Science, Fujian Agriculture and Forestry University, Fuzhou, Fujian, China.
² National Engineering Research Center of Juncao Technology, Fujian Agriculture and Forestry University, Fuzhou, Fujian, China.
³ Hunan University of Humanities, Science, and Technology, Loudi, Hunan, China.

Abstract

Ganoderma lucidum polysaccharide peptide (GLPP) is one of the most abundant constituents of Ganoderma lucidum (G. lucidum), with a wide range of functional activities. The present study investigated the immunomodulatory effects of GLPP in cyclophosphamide (CTX)-induced immunosuppressive mice. The results showed that 100 mg/kg/day of GLPP administration significantly alleviated CTX-induced immune damage by improving immune organ indexes, earlap swelling rate, the index of carbon phagocytosis and clearance value, secretion of cytokines (TNF-α, IFN-γ, and IL-2), and immunoglobulin A(IgA) in the mice. Furthermore, ultra-performance liquid chromatography with mass/mass spectrometry (UPLC-MS/MS) was conducted to identify the metabolites, followed by biomarker and pathway analysis. The results showed that GLPP treatment alleviated CTX-induced alterations in the fecal metabolome profile, including arachidonic acid (AA), leukotriene D4 (LTD4), indole-3-ethanol, and formyltetrahydrofolate (CF), by reversing citric acid, malic acid, cortisol, and oleic acid. These results support the concept that GLPP exhibits immunomodulatory activity via the folate cycle, methionine cycle, TCA cycle, fatty acid biosynthesis and metabolism, glycerophospholipid metabolism, AA metabolism, and cAMP pathways. In conclusion, the results could be helpful to understand the use of GLPP to clarify the immunomodulatory mechanism and be used as immunostimulants to prevent CTX-induced side effects in the immune system.

Keywords: Ganoderma lucidum polysaccharide peptide; UPLC-MS/MS; cyclophosphamide-induced mice; fecal metabolome; immunomodulatory.

Grants and funding

This work was supported by a grant from the Central Government-Guided Local Science and Technology Development Projects (2021L3008), the Major Special Project of Fujian Province, Research and Application of Key Technologies for Innovation and Industrialized Utilization of Juncao (2021NZ029009), and Interdisciplinary Integration to Promote the High-Quality Development of Juncao Science and Industry (XKJC-712021030).